Percent Change In Cerebral Blood Flow Research Articles

OR31-03 Testosterone Gender-affirming Hormonal Therapy Is Associated With Decreased Cerebral Blood Flow In Transgender Teens

Abstract Disclosure: S. Cote: None. K. Fathy: None. S. Lenet: None. O. Espinosa-Bentancourt: None. E. Lavallee: None. E. Croteau: None. D. Rottembourg: None. J. Lepage: None. K. Whittingstall: None. There is increasing demand for gender-affirming hormonal therapy (GAHT) in recent years, with increased access to GAHT for transgender teenagers. While it is well documented that psychological outcomes and quality of life improve after GAHT, it remains unclear how cerebrovascular physiology changes with GAHT. Therefore, this study aimed to investigate the effects of testosterone GAHT on cerebral microvascular and macrovascular physiology in teenage transgender men receiving GAHT. Six teenage transgender men were referred by their endocrinologist prior to the start of GAHT. Participants visited the research center before GAHT (session 1) and between 3 to 9 months into their GHAT (session 2). At each visit, participants completed a non-contrast-enhanced magnetic resonance imaging (MRI) protocol. This protocol assessed the macrovasculature using time-of-flight magnetic resonance angiography to visualize cerebral arteries and estimate diameters of the Circle of Willis and 2D-Phase Contrast to estimate large artery blood velocity. The microvasculature was assessed using pseudo-Continuous Arterial Spin Labelling, which estimates cerebral blood flow (CBF). Paired-sample t-tests were performed between sessions to determine if arterial diameters, CBF and blood velocity change with GAHT. Whole-brain CBF significantly decreased with GAHT between session 1 and session 2 (CBFS1=69.15 +/- 5.85 ml/100g/min; CBFS2=59.30 +/- 8.11 ml/100g/min; t=3.19, p=0.02, df=5). The average percent change in CBF was -9.85%, and the largest decrease experienced by a participant was -20.44%. Note that even though CBF decreased, average whole-brain CBF for all participants remained in a healthy range. We observed no significant change in large artery blood velocity or arterial lumen diameters of the Circle of Willis after starting GAHT. Our results suggest that GAHT influences the brain’s microvasculature. As women tend to have higher CBF than men, the reduction in CBF likely reflects a masculinization of the brain with GAHT. Without EEG to probe neuronal activity, it is difficult to determine if the change is due to decreased neuronal activity or a structural and/or functional change in the microvasculature. Considering that little is known about the long-term effects of GAHT on the brain, these results highlight the need to better understand how hormonal states impact human cerebrovascular physiology and how it may relate to risk for cerebrovascular disease and neurological disorders. Presentation: Sunday, June 18, 2023

The use of novel diffuse optical spectroscopies for improved neuromonitoring during neonatal cardiac surgery requiring antegrade cerebral perfusion.

Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO2) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure. Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO2) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP. During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min (n = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO2 during ACP. This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates.

Abstract 193: Real-time Quantitative Changes in Cerebral Blood Flow From Intra-arterial Vasodilator Treatment in Cerebral Vasospasm

Introduction: Intra-arterial (IA) vasodilators are key components in the treatment of cerebral vasospasm (CV) resulting from subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI). Angiographic assessments of vessel caliber immediately after infusion, however, are unreliable metrics of treatment effect, and as a result there does not currently exist a clear biomarker against which to titrate treatment. Quantitative cerebral blood flow (CBF) measurements from angiographic images may better characterize treatment effect and provide real-time feedback to guide infusion protocols. Methods: From our prospectively maintained institutional registry, we identified patients treated with IA vasodilators in the anterior circulation for CV between July 2014 and June 2016. Angiograms were reviewed by an experienced neuro angiographer blinded to clinical data and subsequent imaging. Regions of interest (ROIs) were drawn by two experienced neuroimagers over the MCA territory. CBF maps were calculated automatically from immediate pre- and immediate post-infusion angiograms using perfusion angiography and averaged over the ROIs. Results: A total of 65 angiograms were evaluated from 22 patients treated with vasodilators for CV. Average age was 48 and 60% were female. Etiology of vasospasm included SAH in 83% (54/65), TBI in 14% (9/65) and stroke/vasculopathy in 3% (2/65) Degree of vasospasm varied from mild (20% (13/65)) to moderate ((62% (40/65)) and severe (18% (12/65)). All patients were treated with IA verapamil ranging from 5 mg to 30 mg over the course of 10-60 minutes. Immediate post-infusion angiograms demonstrated improved vascular caliber in 23% (15/65) cases. In comparison, CBF increased on average 11% (SD 49) after verapamil infusion. Verapamil dosage correlated with percent change in CBF (p<0.05, Spearman’s correlation). Conclusions: Verapamil infusion resulted in increased CBF in patients with CV from SAH and TBI. Quantitative angiographic CBF may serve as an effective real-time biomarker of treatment efficacy.

Comparison of Cerebral Vascular Reactivity Measures Obtained Using Breath-Holding and CO2 Inhalation

Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO2 (PETCO2). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO2 for prospective targeting of PETCO2, (2) administration of a fixed concentration of CO2 leading to subject-dependent changes in PETCO2, (3) a breath-hold (BH) paradigm with physiologic modeling of CO2 accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in PETCO2, methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100 g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO2 dose-response curve, avoiding hypocapnic conditions.

Autoregulation after ischaemic stroke

Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced. Nine participants, 1-11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 +/- 7 mmHg and CBF measurement was repeated. Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres. In this study, selective regional impairment of CBF autoregulation in the infarcted hemisphere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome.

Regional cerebral blood flow during acute hypoxia in individuals susceptible to acute mountain sickness

Individuals susceptible to high altitude pulmonary edema show altered pulmonary vascular responses within minutes of exposure to hypoxia. We hypothesized that a similar acute-phase vulnerability to hypoxia may exist in the brain of individuals susceptible to acute mountain sickness (AMS). In established AMS and high altitude cerebral edema, there is a propensity for vasogenic white matter edema. We therefore hypothesized that increased cerebral blood flow (CBF) during acute hypoxia would also be disproportionately greater in white matter (WM) than grey matter (GM) in AMS-susceptible subjects. We quantified regional CBF using arterial spin labeling MRI during 30 min hypoxia (F(I)O(2) = 0.125) in two groups: AMS-susceptible (AMS-S, n = 6) who invariably experienced AMS at altitude, and AMS-resistant (AMS-R, n = 6) who never experienced AMS despite multiple rapid ascents to high altitude. SaO(2) during hypoxia did not differ between groups (AMS-S = 87+/-4%, AMS-R = 89+/-3%, p = 0.3). Steady-state whole-brain CBF increased in hypoxia (p<0.005), but did not differ between groups (normoxia: AMS-S = 42.7+/-14.0 ml/(100 g min), AMS-R = 41.7+/-10.1 ml/(100 g min); hypoxia: AMS-S = 47.8+/-19.5 ml/(100 g min), AMS-R = 48.2+/-10.1 ml/(100 g min), p = 0.65), and cerebral oxygen delivery remained constant. The percent change in CBF did not differ between brain regions or between groups (although absolute CBF change was greater in GM): (GM: AMS-S = 6.1+/-7.7 ml/(100 g min) (10+/-11%), AMS-R = 8.3+/-5.7 ml/(100 g min) (17+/-11%), p = 0.57; WM: AMS-S = 4.3+/-5.1 ml/(100 g min) (12+/-15%), AMS-R = 4.8+/-2.9 ml/(100 g min) (16+/-9%), p = 0.82). CBF increases in acute hypoxia, but is not different between WM and GM, irrespective of AMS susceptibility. Acute phase differences in regional CBF during acute hypoxia are not a primary feature of susceptibility to AMS.

Continuous Arterial Spin Labeled Perfusion Magnetic Resonance Imaging in Patients before and after Carotid Endarterectomy

Continuous arterial spin labeling perfusion magnetic resonance imaging (CASL-pMRI) uses magnetically labeled arterial blood water as a tracer to obtain quantifiable measurements of cerebral blood flow (CBF) (mL/100 g-1/min-1). CASL-pMRI was used to assess CBF changes in major vascular distributions in patients (n = 10) prior to and 3 months after carotid endarterectomy (CEA). No significant change in the global baseline CBF before and after CEA was observed in the group as a whole (P = .81). In patients with reduced CBF prior to CEA (< 50 ml/100 g/min), a significant increase in global CBF following CEA was observed. An inverse relationship existed between percent change in CBF after CEA versus baseline CBF within the anterior circulation (r = -.78, P < .05) but not in the posterior distribution (r = .25, P = .63). CASL-pMRI may provide a convenient, inexpensive, noninvasive method for identifying CEA patients at risk for hyperperfusion following carotid revascularization.

Reduced blood flow response to acetazolamide reflects pre-existing vasodilation and decreased oxygen metabolism in major cerebral arterial occlusive disease

A decrease in the cerebral blood flow (CBF) response to acetazolamide may indicate an increase in cerebral blood volume (CBV) caused by reduced perfusion pressure in patients with major cerebral artery steno-occlusive lesions. However, a decrease in cerebral metabolic rate of oxygen (CMRO(2)) caused by ischemic changes may also decrease the CBF response to acetazolamide by decreasing the production of carbon dioxide. The purpose of this study was to determine whether the values of CBV and CMRO(2) are independent predictors of the CBF response to acetazolamide in major cerebral arterial occlusive disease. We used positron emission tomography to study 30 patients with major cerebral artery steno-occlusive lesions. The CBF response to acetazolamide was assessed by measuring baseline CBF and CBF 10 min after an intravenous injection of 1 g of acetazolamide. Multivariate analysis was used to test the independent predictive value of the CBV and CMRO(2) at baseline with respect to the percent change in CBF during acetazolamide administration. Both increased CBV and decreased CMRO(2) were significant and independent predictors of the reduced CBF response to acetazolamide. CBV accounted for 25% of the variance in the absolute change in CBF during acetazolamide administration and 42% of the variance in the percent change in CBF, whereas CMRO(2) accounted for 19% and 4% of the variance, respectively. In patients with major cerebral arterial occlusive disease, a decrease in CMRO(2) may contribute to the reduced CBF response to acetazolamide, although an increase in CBV appears to be the major contributing factor.

Intra-arterial nitrovasodilators do not increase cerebral blood flow in angiographically normal territories of arteriovenous malformation patients.

The mechanism of adaptation to chronic cerebral hypotension in normal brain adjacent to cerebral arteriovenous malformations (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow (CBF) studies in structurally and functionally normal vascular territories during 53 distal cerebral angiographic procedures in 37 patients with AVMs. CBF was measured using the superselective intra-arterial 133Xe method before and after a 3-minute infusion of either verapamil (1 mg.min-1, n = 23), acetylcholine (1.33 micrograms.kg-1.min-1, n = 7), nitroprusside (0.5 microgram.kg-1.min-1, n = 16) or nitroglycerin (0.5 microgram.kg-1.min-1, n = 7). Mean +/- SD systemic (76 +/- 13 mm Hg) and distal cerebral arterial (55 +/- 16 mm Hg; range, 20 to 97 mm Hg) pressures were not different among groups. Verapamil increased CBF (45 +/- 12 to 65 +/- 21 mL.100 g-1.min-1, P < .001). There was no effect of acetylcholine (no change [46 +/- 9 to 46 +/- 9 mL.100 g-1.min-1], NS) or nitroglycerin (36 +/- 14 to 36 +/- 13 mL.100 g-1.min-1, NS). Nitroprusside decreased CBF (40 +/- 12 to 31 +/- 11 mL.100 g-1.min-1, P < .001). The percent change in CBF after drug administration was proportional to cerebral arterial pressure for verapamil only (r = .57, P = .0051). When infused intra-arterially in clinically relevant doses in both hypotensive and normotensive normal vascular territories remote from an AVM nidus, calcium channel blockade caused vasodilation, but there was an absence of response to nitric oxide-mediated vasodilators. These data suggest that (1) the nitric oxide pathway probably is not involved in the adaptation to chronic cerebral hypotension in AVM patients and (2) if our findings in vessels remote from or contralateral to the AVM are applicable to vessels of patients with other forms of cerebrovascular disease, clinically relevant doses of intra-arterial nitrovasodilators may not be useful in the manipulation of cerebrovascular resistance.

Cerebrovascular response in infants and young children following severe traumatic brain injury: a preliminary report.

To further describe the pathophysiologic processes that occur in infants and young children after severe traumatic brain injury (TBI), we retrospectively reviewed the cerebral blood flow (CBF) values and 6-month Glasgow Outcome Scores (GOS) in 30 children < or = 8 years old (25 were < or = 4 years old) with a Glasgow Coma Score (GCS) on admission of < or = 8. Twelve females and 18 males (mean age 2.1 years, range 1 month to 8 years) underwent 61 CBF studies using stable xenon computed tomography at variable times from admission to 9 days after TBI. In 12 patients, PaCO2 was manipulated an average of 8.4 torr (range 5-11 torr) and a second CBF study performed to determine CO2 vasoreactivity (CO2VR), defined as the percent change in CBF per torr change in PaCO2. CBF on admission (n = 13)was 25.1+/-7.7 ml/100 g/min (mean +/- SEM) and was < or = 20 ml/100 g/min in 10 of 13 patients (77%). By 24 h and for up to 6 days after TBI, the mean CBF increased to 55.3+/-3.4 ml/100 g/min (range 2-95) which differed significantly from the admission CBF value (p < 0.05); a CBF of >70 ml/100 g/min tended to be associated with a good outcome. Poor outcome (GOS < or = 3) was seen uniformly in children under the age of 1 year and in patients with a CBF of < or = 20 ml/100 g/min any time after TBI. Poor outcome was seen in 85% of children under the age of 24 months, but in only 41% of children > or = 24 months old. Mean CO2VR was 2.1+/-0.6%/torr PaCO2 and ranged from 0.02 to 5.98%. Mean CO2VR tended to differ between good and poor outcome children (3.2+/-0.9 and 1.17+/-0.2%, respectively) and a CO2VR of < or = 2% was significantly associated with a poor outcome. Younger age, low CBF in the early period after TBI, and a CO2VR of <2% was associated with a poor outcome in this subgroup of children. Young children (<24 months) may represent a particular high-risk group with early hypoperfusion after severe TBI. This finding may be a key factor in the pathophysiology and outcome in this age group, and may need to be addressed in our future therapeutic protocols.

Internal jugular bulb blood velocity as a continuous indicator of cerebral blood flow during open heart surgery.

Most techniques for measuring cerebral blood flow (CBF) can not be performed rapidly enough to detect sudden changes in CBF. However, measurement of internal jugular bulb (IJB) blood velocity may offer real-time information on changes in CBF. In the current study, we measured IJB blood velocity and CBF in anesthetized humans. In protocol 1, IJB blood velocity was continuously measured using an intravascular Doppler catheter during cardiac surgery under hypothermic cardiopulmonary bypass (CPB). CBF values obtained with a Kety-Schmidt method using inhalation of 30% argon in oxygen gas were compared with concurrent IJB blood velocity values in ten patients. A 3-French intravascular Doppler catheter was placed in the right IJB, and CBF measurements were made before CPB, in a stable hypothermic period during CPB, at rewarming during CPB, and after CPB. In protocol 2, dimensions of right IJB were observed before and during CPB using an intravascular rotating A scan ultrasonic catheter (5-French) in three patients. IJB blood velocity responded quickly to changes in arterial pressure or body temperature during CPB. The percent change in IJB blood velocity relative to pre-CPB value showed a good linear correlation with the percent change in CBF (%CBF = 0.87 x %IJB velocity + 17, r = 0.87). The mean difference between percent changes in CBF and IJB blood velocity was -5.6% and the standard deviation was 16%. Despite a large reduction in arterial pressure or IJB pressure, there were no significant changes in the IJB dimension. The results suggest that IJB blood velocity may represent a clinically useful monitor of changes in CBF in anesthetized humans.